Skin cancer is the most common type of cancer in the US. Approximately 1,000,000.0 Americans are diagnosed with it every year, with a death rate of ˜2,000.0/year. According to the U.S. National Institute of Health, ultraviolet (UV) radiation from the sun is the main cause of skin cancer. Artificial sources can also cause skin cancer. The risk of developing skin cancer is also related to the place where the person lives. People who live in areas that receive high levels of UV radiation from the sun are more likely to develop skin cancer. In the United States, skin cancer is more common in Texas and Florida than it is in Minnesota or Wyoming. Worldwide, the places with highest rates of skin cancer are South Africa and Australia.
There are several types of tumor tissue in the skin that may or may not be able to spread to other tissues and pose a serious life threat (metastasis). There are mainly three malign tumor conditions of the skin: Malignant Melanoma (MM), Basal Cell Carcinoma (BCC), and Squamous Cell Carcinoma (SCC). MM can metastasize rapidly, it is diagnosed correctly with about 75% efficiency, by a trained dermatologist. Melanoma is the most serious form of skin cancer; about 60,000 people will be diagnosed with it in the US, this year (2009). BCC is the most common skin tumor, it does not metastasize. There is 65% correct diagnosis of BCC for practicing dermatologists. Some of the benign tumor tissues are known as Seborrhoeic Keratosis (SK) and Pigmented Nevi (NV). One of the important tasks of any diagnostics tool for skin cancer is to be able to discriminate between these five different tissue conditions.
The gold standard for detection and diagnosis of Melanoma is histopathology. This procedure is performed on a biopsy sample by a specialized dermatologist. Although it is highly subjective, it can be stated that on average, for malignant Melanoma, this procedure has an 80% sensitivity (percent of positive measurements, relative to sampling universe). The specificity of the technique (percent of true positives plus true negatives, relative to sampling universe) usually varies from 40% to 80%, depending on the level of expertise of the clinical staff. The overall efficacy of the technique, defined as the product, specificity×sensitivity is therefore well below 0.6 (60%). This procedure is highly invasive, time consuming, uncomfortable and costly. Added to the intrinsic cost of the procedure is the fact that between 95% to 98% of them result in negative diagnostics, meaning that the incurred cost was essentially unnecessary. The problem at hand therefore consists in the development of a diagnostics technique that is objective and repeatable, non-invasive, has low cost, and out-performs the dermatologist's sensitivity and specificity for the measurement. Furthermore, there is a solid potential for using this device in other types of cancerous malignancies in different tissues, or in a more sophisticated configuration, like a microscopic imaging device.
Raman spectroscopy is a proven technology in biomedical, chemical, industrial and other sensing applications. However, significant problems exist for implementing this technique, such as detector sensitivity, processing speed, simultaneous multi-component analysis of a single sample, environmental ruggedness, and cost. In order to obtain Raman spectra from a sample, a high intensity optical source is needed (typically a laser) to pump the inelastic Raman scattering process within the material, be it a gas, a liquid, or a solid. As a result, the material scatters radiation in all directions, at different frequencies. The component with frequency equal to that of the pump laser corresponds to Rayleigh scattering, and the component with frequency shifted lower than that of the pump laser is called Stokes radiation, a portion of which corresponds to Raman scattering. The main feature of Raman scattering is that it occurs regardless of the wavelength of the pumping optical source, while keeping the frequency shift between Stokes and pump radiation fixed. The Stokes radiation shift and intensity are dependent upon the material. Typically, Stokes Raman shifts are in the order of a few to tens of tera-Hertz (THz), and their intensity is 4 to 5 orders of magnitude lower than the Rayleigh scattered light. In order to discriminate and measure accurately the Raman scattered radiation from the Rayleigh radiation, a blocking filter for the Rayleigh frequency needs to be used in all Raman measurement systems. Fortunately, the typical Raman Stokes shift is large enough to allow for current state-of-the-art filters to block the Rayleigh radiation while marginally affecting the Raman Stokes radiation.
Time-resolved Raman spectroscopy techniques have been used for years. Detection and analysis of the signal in these systems is typically difficult and expensive. Commercial Raman spectrometers are:
1) too slow for many practical applications, with signal processing time of a few seconds or more. Real-time process monitoring is impossible, as are many medical and in-vivo applications;
2) typically limited to measuring no more than two or three components within a given sample, at a time, due to high spectral overlap between different analytes;
3) physically sensitive to the environment such as movement, vibration, and temperature changes, in their performance; and
4) not optically sensitive for many applications such as detecting weak markers in biological samples or weak returns and noisy signals from long-range sensing applications.
Techniques for processing multiple components, in the order of 20 to 100, with a 1 to 10 second typical collection for each, require an excessive amount of time to complete a full sample analysis. Weak signals from noisy environments result in the loss of important spectral information in many cases. Field applications in harsh environments are also off limits for currently available Raman systems.
The most popular types of spectrometers in use today are Fourier-Transform type devices. Fourier Transform Infra-red (FTIR) and Fourier Transform Raman (FTR) spectrometers employ a motor to create a linear displacement of sensitive optical elements in the detection process. This technique has serious operational and environmental limitations, since alignment must be maintained as optical parts are being moved, and also time-calibration is necessarily complex since non-uniform linear motion is involved.
Accordingly, there is a need for simple, environmentally insensitive Raman spectrometers capable of determining multiple components in a sample within a very short time. There is also a need for a reliable and simple mechanism for performing skin analysis that can adequately determine whether or not a biopsy needs to be collected from an individual in order to determine if certain portion of the skin is affected by a pathologic condition that requires immediate attention, like malignant melanoma.